Novel Sequential Therapy with Obinutuzumab and Telitacicept in Severe Lupus Nephritis with Glucocorticoid-Induced Avascular Necrosis (AVN) of the Femoral Head: A Case Report

BACKGROUND Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease characterized by immune-mediated inflammation. Nearly half of SLE patients develop lupus nephritis (LN). Glucocorticoids are the most widely used foundational medication for SLE, yet their long-term use leads to a series of complications, such as opportunistic infections, diabetes, and femoral head osteonecrosis. Obinutuzumab is a humanized anti-CD20 monoclonal antibody, whereas telitacicept is a fusion protein that blocks B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL). Since monotherapy with B-cell depletion agents may lead to disease flare due to B-cell reconstitution and elevated levels of B-cell-stimulating factors (eg, BAFF), a new combination therapy involving B-cell depletion and BAFF/APRIL inhibitors could be an alternative to conventional therapies for patients, especially those with severe SLE. This combination has not yet been clinically applied. CASE REPORT We report the case of a 22-year-old woman with biopsy-proven class V LN 6 years ago, initially managed with prednisone, tacrolimus, and hydroxychloroquine. She developed glucocorticoid-induced femoral head necrosis 2 years after diagnosis and experienced recurrent lupus flares requiring multiple hospitalizations. At this admission for a critically severe lupus flare (SLEDAI score: 27), sequential treatment with Obinutuzumab followed by telitacicept resulted in effective remission of lupus activity. CONCLUSIONS This is the first reported case of severe SLE treated with sequential therapy involving Obinutuzumab followed by telitacicept. The combination therapy of B-cell depletion plus BAFF/APRIL inhibition could be a promising and rational treatment approach for SLE patients, especially those with severe SLE, which warrants further clinical trials to validate the efficacy and safety of the therapeutic regimen.